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Transcriptomic hallmarks of tumor‐stromal interactions in brain metastasis
Author(s) -
Nguyen Don
Publication year - 2018
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2018.32.1_supplement.39.4
Subject(s) - brain metastasis , stromal cell , metastasis , epigenetics , tumor microenvironment , transcriptome , biology , circulating tumor cell , cancer research , cancer , ex vivo , in vivo , neuroscience , gene expression , gene , tumor cells , biochemistry , genetics , microbiology and biotechnology
The central nervous system (CNS) is a major site of relapse for several types of treatment refractory cancers including tumors from the lung, skin, and breast. The incidence of brain metastasis associated deaths is rising, because of the limited delivery of drugs across the blood brain barrier (BBB) and morbidity of metastasis once spread in the CNS. One of the most rate limiting steps of CNS metastasis is the ability of disseminated tumor cells (DTC) to outgrow after extravasating across the BBB. Deciphering the molecular interactions which dictate this step in vivo remains a challenge due to the heterogeneous patterns of tumor outgrowth in the CNS and the unique nature of this tumor microenvironment (TME). To address this challenge, we optimized a novel method for RNA sequencing analysis which leverages xenograft models and overcomes the confounding analytic effects incurred during the isolation of cells ex‐vivo . Using this method, we could decipher molecular alterations that are specific to the tumor cells or the stroma in situ with increased accuracy and sensitivity, revealing striking new insights into brain‐specific transcriptional co‐adaptation of malignant cells and their neuroinflammatory milieu. These gene expression programs are linked to specific patterns of metastatic outgrowth, anatomical location in the brain, and interaction with neuronal cell types. Our study provides a molecular framework to understand the heterogeneous biological manifestation of brain metastasis while revealing novel epigenetic and phenotypic state(s) utilized by metastatic cells to persist and outgrow in the CNS. Support or Funding Information This study was funded by grants from the National Cancer Institute (R01CA166376 and R01CA191489). This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .